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https://www.readbyqxmd.com/read/29656318/a-novel-tetrasubstituted-imidazole-as-a-prototype-for-the-development-of-anti-inflammatory-drugs
#1
Marcus Vinicius P S Nascimento, Antonio C M Munhoz, Lais C Theindl, Eduarda Talita B Mohr, Najla Saleh, Eduardo B Parisotto, Thaís A Rossa, Ariane Zamoner, Tania B Creczynski-Pasa, Fabíola B Filippin-Monteiro, Marcus M Sá, Eduardo Monguilhott Dalmarco
Although inflammation is a biological phenomenon that exists to protect the host against infections and/or related problems, its unceasing activation results in the aggravation of several medical conditions. Imidazoles, whether natural or synthetic, are molecules related to a broad spectrum of biological effects, including anti-inflammatory properties. In this study, we screened eight novel small molecules of the imidazole class synthesized by our research group for their in vitro anti-inflammatory activity...
April 14, 2018: Inflammation
https://www.readbyqxmd.com/read/29655691/functionalized-liposomes-and-phytosomes-loading-annona-muricata-l-aqueous-extract-potential-nanoshuttles-for-brain-delivery-of-phenolic-compounds
#2
Simona Mancini, Luca Nardo, Maria Gregori, Inês Ribeiro, Francesco Mantegazza, Cristina Delerue-Matos, Massimo Masserini, Clara Grosso
BACKGROUND: Multi-target drugs have gained significant recognition for the treatment of multifactorial diseases such as depression. Under a screening study of multi-potent medicinal plants with claimed antidepressant-like activity, the phenolic-rich Annona muricata aqueous extract (AE) emerged as a moderate monoamine oxidase A (hMAO-A) inhibitor and a strong hydrogen peroxide (H2 O2 ) scavenger. PURPOSE: In order to protect this extract from gastrointestinal biotransformation and to improve its permeability across the blood-brain barrier (BBB), four phospholipid nanoformulations of liposomes and phytosomes functionalized with a peptide ligand promoting BBB crossing were produced...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29655499/genetic-testing-in-clinical-settings
#3
Nora Franceschini, Amber Frick, Jeffrey B Kopp
Genetic testing is used for screening, diagnosis, and prognosis of diseases consistent with a genetic cause and to guide drug therapy to improve drug efficacy and avoid adverse effects (pharmacogenomics). This In Practice review aims to inform about DNA-related genetic test availability, interpretation, and recommended clinical actions based on results using evidence from clinical guidelines, when available. We discuss challenges that limit the widespread use of genetic information in the clinical care setting, including a small number of actionable genetic variants with strong evidence of clinical validity and utility, and the need for improving the health literacy of health care providers and the public, including for direct-to-consumer tests...
April 11, 2018: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/29653190/evaluation-of-whole-genome-sequencing-and-software-tools-for-drug-susceptibility-testing-of-mycobacterium-tuberculosis
#4
Janko van Beek, Marjo Haanperä, Pieter W Smit, Silja Mentula, Hanna Soini
OBJECTIVES: Culture-based assays are currently the gold standard for drug susceptibility testing (DST) for Mycobacterium tuberculosis. They provide good sensitivity and specificity, but are time-consuming. The objective of this study was to evaluate whether whole genome sequencing (WGS), combined with software tools for data analysis, can replace routine culture based assays for drug susceptibility testing of M. tuberculosis. METHODS: M. tuberculosis cultures sent to the Finnish mycobacterial reference laboratory in 2014 (n=211) were phenotypically tested by Mycobacteria Growth Indicator Tube (MGIT) for first line drug susceptibilities...
April 10, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29653073/a-zebrafish-heart-failure-model-for-assessing-therapeutic-agents
#5
Xiao-Yu Zhu, Si-Qi Wu, Sheng-Ya Guo, Hua Yang, Bo Xia, Ping Li, Chun-Qi Li
Heart failure is a leading cause of death and the development of effective and safe therapeutic agents for heart failure has been proven challenging. In this study, taking advantage of larval zebrafish, we developed a zebrafish heart failure model for drug screening and efficacy assessment. Zebrafish at 2 dpf (days postfertilization) were treated with verapamil at a concentration of 200 μM for 30 min, which were determined as optimum conditions for model development. Tested drugs were administered into zebrafish either by direct soaking or circulation microinjection...
March 20, 2018: Zebrafish
https://www.readbyqxmd.com/read/29651943/benzoin-schiff-bases-design-synthesis-and-biological-evaluation-as-potential-antitumor-agents
#6
Dima A Sabbah, Fatima Al-Tarawneh, Wamidh H Talib, Kamal Sweidan, Sanaa K Bardaweel, Eveen Al-Shalabi, Haizhen A Zhong, Ghassan Abu Sheikha, Reema Abu Khalaf, Mohammad S Mubarak
BACKGROUND: Phosphoinositide 3-kinase α (PI3Kα) is an attractive target for anticancer drug design. OBJECTIVES: Target compounds were designed to probe the significance of alcohol and imine moieties tailored on a benzoin scaffold to better understand the structure activity relation (SAR) and improve their biological activity as anticancer compounds. METHODS: Chemical synthesis of the targeted compounds, biological evaluation tests against human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines, as well as Glide docking studies were employed in this investigation...
April 12, 2018: Medicinal Chemistry
https://www.readbyqxmd.com/read/29651937/an-emerging-role-of-endometrial-inflammasome-in-reproduction-new-therapeutic-approaches
#7
Fiorella Di Nicuolo, Monia Specchia, Lorenza Trentavizi, Giovanni Scambia, Nicoletta Di Simone
One of the common complications of pregnancy is spontaneous pregnancy loss which occurs in an estimated 5- 15% of pregnancies. Of all women 1%-5% suffer from recurrent pregnancy loss (RPL). Despite the fact that RPL has been associated to various anatomic, hormonal, immune, hematologic, and genetic defects, in 30% of the patients, screening tests included in the RPL workup may have negative results. Recently, we demonstrated a significant increased activation of endometrial NALP-3 inflammasome, and a caspase-1 dependent secretion of IL-18 and IL-1β in the endometrial tissues obtained from RPL women compared with a fertile women group...
April 12, 2018: Protein and Peptide Letters
https://www.readbyqxmd.com/read/29651932/alternative-host-models-for-testing-anti-protozoal-or-antifungal-compounds-and-fungal-infection
#8
Ana Claudia Torrecilhas, Patricia Xander, Karen Spadari Ferreira, Wagner Luiz Batista
The neglected tropical diseases (NTDs) are caused by several parasites, fungi, bacteria and viruses and affect more than one billion people in the world. The control and prevention against NTDs need implementation of alternative methods for testing new compounds against these diseases. For the implementation of alternative methods, it is necessary to apply the principles of replacement, reduction and refinement (the 3Rs) for the use of laboratory animals. Accordingly, the present review addressed a variety of alternative models to study the infections caused by protozoa and fungi...
April 12, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29651095/validation-of-ultrasound-bioimaging-to-predict-worm-burden-and-treatment-efficacy-in-preclinical-filariasis-drug-screening-models
#9
Amy E Marriott, Hanna Sjoberg, Hayley Tyrer, Joanne Gamble, Emma Murphy, John Archer, Andrew Steven, Mark J Taylor, Joseph D Turner
Filariasis is a global health problem targeted for elimination. Curative drugs (macrofilaricides) are required to accelerate elimination. Candidate macrofilaricides require testing in preclinical models of filariasis. The incidence of infection failures and high intra-group variation means that large group sizes are required for drug testing. Further, a lack of accurate, quantitative adult biomarkers results in protracted timeframes or multiple groups for endpoint analyses. Here we evaluate intra-vital ultrasonography (USG) to identify B...
April 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29642892/a-systematic-and-prospectively-validated-approach-for-identifying-synergistic-drug-combinations-against-malaria
#10
Yasaman KalantarMotamedi, Richard T Eastman, Rajarshi Guha, Andreas Bender
BACKGROUND: Nearly half of the world's population (3.2 billion people) were at risk of malaria in 2015, and resistance to current therapies is a major concern. While the standard of care includes drug combinations, there is a pressing need to identify new combinations that can bypass current resistance mechanisms. In the work presented here, a combined transcriptional drug repositioning/discovery and machine learning approach is proposed. METHODS: The integrated approach utilizes gene expression data from patient-derived samples, in combination with large-scale anti-malarial combination screening data, to predict synergistic compound combinations for three Plasmodium falciparum strains (3D7, DD2 and HB3)...
April 11, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29642875/comparing-the-performance-of-circulating-cathodic-antigen-and-kato-katz-techniques-in-evaluating-schistosoma-mansoni-infection-in-areas-with-low-prevalence-in-selected-counties-of-kenya-a-cross-sectional-study
#11
Collins Okoyo, Elses Simiyu, Sammy M Njenga, Charles Mwandawiro
BACKGROUND: Kato-Katz technique has been the mainstay test in Schistosoma mansoni diagnosis in endemic areas. However, recent studies have documented its poor sensitivity in evaluating Schistosoma mansoni infection especially in areas with lower rates of transmission. It's the primary diagnostic tool in monitoring impact of the Kenya national school based deworming program on infection transmission, but there is need to consider a more sensitive technique as the prevalence reduces. Therefore, this study explored the relationship between results of the stool-based Kato-Katz technique with urine-based point-of-care circulating cathodic antigen (POC-CCA) test in view to inform decision-making by the program in changing from Kato-Katz to POC-CCA test...
April 11, 2018: BMC Public Health
https://www.readbyqxmd.com/read/29642834/-risk-of-travel-associated-tuberculosis
#12
Süheyla Sürücüoğlu
Tuberculosis has spread by human movements throughout history. There have been reports indicating tuberculosis transmission on all travel vehicles, including aircrafts, ground vehicles and vessels until today. However, due to the ever increasing of air transportation and air travelling among countries with low and high tuberculosis incidence, transmission risk especially in aircrafts has become an important issue worldwide. But in many of the studies conducted in this regard, transmission of tuberculosis in aircrafts was found very low...
January 2018: Mikrobiyoloji Bülteni
https://www.readbyqxmd.com/read/29628190/prognostic-utility-of-initial-lactate-in-patients-with-acute-drug-overdose-a-validation-cohort
#13
Randy Cheung, Robert S Hoffman, David Vlahov, Alex F Manini
STUDY OBJECTIVE: Previous studies have suggested that the initial emergency department (ED) lactate concentration may be an important prognostic indicator for inhospital mortality from acute drug poisoning. We conduct this cohort study to formally validate the prognostic utility of the initial lactate concentration in a larger, distinct patient population with acute drug overdose. METHODS: This observational, prospective, cohort study was conducted during 5 years at 2 urban teaching hospitals...
April 6, 2018: Annals of Emergency Medicine
https://www.readbyqxmd.com/read/29627719/interference-of-doacs-in-different-drvvt-assays-for-diagnosis-of-lupus-anticoagulants
#14
T Flieder, M Weiser, Th Eller, M Dittrich, K von Bargen, S Alban, J Kuhn, C Knabbe, I Birschmann
OBJECTIVE: Determination of lupus anticoagulants (LA) is an important, but still challenging test in the diagnosis of antiphospholipid syndrome (APS). This is especially the case in patients using one of the direct oral anticoagulants (DOACs). The aim of our study was to examine the influence of these drugs on DRVVT assays from two companies (in each case: screening test, confirming test and calculated ratio) and on aPTT and lupus-sensitive aPTT. METHODS: We used plasma samples from healthy volunteers spiked with the DOACs dabigatran, rivaroxaban and apixaban (0, 10, 30, 50, 100 ng/mL) for testing...
March 21, 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29626744/opioids-in-oral-fluid-of-spanish-drivers
#15
Francisco Herrera-Gómez, Mercedes García-Mingo, Mónica Colás, Juan Carlos González-Luque, F Javier Álvarez
BACKGROUND: Driving under the influence of certain drugs is not allowed, and roadside drug testing is being considered an important tool for deterring driving under the influence of them. This study aimed to assess the presence and concentration of opioids, as well as their combined use with other drugs (laboratory confirmation after the on-road screening) in Spanish drivers between 2011 and 2016. METHODS: In Spain, mandatory roadside breath alcohol and oral fluid drug testing (screening) are carried out by the Traffic Police using Dräger Alcotest® 6810 device, and Dräger DrugTest® 5000, DrugWipe® , or Alere™ DDS® 2 Mobile Test System...
March 29, 2018: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/29626551/microfluidics-in-nanoparticle-drug-delivery-from-synthesis-to-pre-clinical-screening
#16
Jungho Ahn, Jihoon Ko, Somin Lee, James Yu, YongTae Kim, Noo Li Jeon
Microfluidic technologies employ nano and microscale fabrication techniques to develop highly controllable and reproducible fluidic microenvironments. Utilizing microfluidics, lead compounds can be produced with the controlled physicochemical properties, characterized in a high-throughput fashion, and evaluated in in vitro biomimetic models of human organs; organ-on-a-chip. As a step forward from conventional in vitro culture methods, microfluidics shows promise in effective preclinical testing of nanoparticle-based drug delivery...
April 4, 2018: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29626545/hypoxia-selective-allosteric-destabilization-of-activin-receptor-like-kinases-a-potential-therapeutic-avenue-for-prophylaxis-of-heterotopic-ossification
#17
Guorong Lu, Mary R Tandang-Silvas, Alyssa C Dawson, Trenton J Dawson, Jay C Groppe
Heterotopic ossification (HO), the pathological extraskeletal formation of bone, can arise from blast injuries, severe burns, orthopedic procedures and gain-of-function mutations in a component of the bone morphogenetic protein (BMP) signaling pathway, the ACVR1/ALK2 receptor serine-threonine (protein) kinase, causative of Fibrodysplasia Ossificans Progressiva (FOP). All three ALKs (-2, -3, -6) that play roles in bone morphogenesis contribute to trauma-induced HO, hence are well-validated pharmacological targets...
April 4, 2018: Bone
https://www.readbyqxmd.com/read/29625271/tyrosine-kinase-inhibition-effects-of-novel-pyrazolo-1-5-a-pyrimidines-and-pyrido-2-3-d-pyrimidines-ligand-synthesis-biological-screening-and-molecular-modeling-studies
#18
Mardia T El Sayed, Hoda A R Hussein, Nora M Elebiary, Ghada S Hassan, Shahenda M Elmessery, Ahmed R Elsheakh, Mohamed Nayel, Hatem A Abdel-Aziz
Tyrosine kinases are one of the most critical mediators in the signaling path way. Late studies have proved the part of tyrosine kinases in the pathophysiology of cancer diseases. This current research paper has focused on investigating the novel Pyrazolo[1,5-a]pyrimidines and Pyrido[2,3-d]pyrimidines as a small molecules that can inhibit tyrosine kinase in cancer cells. NCI protocol was applied to test the antitumor activity of such compounds. Leukemia and renal cancer cell lines proved to be sensitive to some derivatives such as 6b-d, 9a and 11 with GI% values ranging from 30...
March 26, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29624387/computer-aided-discovery-and-characterization-of-novel-ebola-virus-inhibitors
#19
Stephen Joseph Capuzzi, Wei Sun, Eugene N Muratov, Carles Martinez-Romero, Shihua He, Wenjun Zhu, Hao Li, Gregory James Tawa, Ethan G Fisher, Miao Xu, Paul Shinn, Xiangguo Qiu, Adolfo García-Sastre, Wei Zheng, Alexander Tropsha
The Ebola virus (EBOV) causes severe human infection that lacks effective treatment. A recent screen identified a series of compounds that block EBOV-like particle entry into human cells. Using data from this screen, Quantitative Structure-Activity Relationship (QSAR) models were built and employed for virtual screening of a ~17 million compound library. Experimental testing of 102 hits yielded 14 compounds with IC50 values under 10 μM, including several sub-micromolar inhibitors, and more than 10-fold selectivity against host cytotoxicity...
April 6, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29623827/comparative-assay-of-2d-and-3d-cell-culture-models-proliferation-gene-expression-and-anticancer-drug-response
#20
Aline G Souza, Isaura Beatriz B Silva, Esther Campos-Fernandez, Leticia S Barcelos, Jessica Brito Souza, Karina Marangoni, Luiz R Goulart, Vivian Alonso-Goulart
In vitro tests allow establishing experimental variables. However, in vitro results cannot be extrapolated to in vivo tests. Considering that three-dimensional (3D) culture has been one of the best ways to portray the in vivo system of most cell types, it is possible to carry out assays with a great clinical relevance for the analysis of the screening, action and resistance of antitumor drugs. Thus, the objective of the present study was to compare between 2D and 3D cell culture forms to conclude which is the most suitable model for preclinical in vitro drug testing...
April 4, 2018: Current Pharmaceutical Design
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